Laboratoire d'Analyse Non Linéaire et Mathématiques Appliquées, University of Tlemcen, Chetouane 13000, Algeria; Univ Lyon, Inria, Université Claude Bernard Lyon 1, CNRS UMR5208, Institut Camille Jordan, F-69603 Villeurbanne, France.
Univ Lyon, Inria, Université Claude Bernard Lyon 1, CNRS UMR5208, Institut Camille Jordan, F-69603 Villeurbanne, France.
J Theor Biol. 2022 Mar 21;537:111005. doi: 10.1016/j.jtbi.2022.111005. Epub 2022 Jan 12.
Bone is a hard-soft biomaterial built through a self-assembly process under genetic regulatory network (GRN) monitoring. This paper aims to capture the behavior of the bone GRN part that controls mineralization by using a mathematical model. Here, we provide an advanced review of empirical evidence about interactions between gene coding (i) transcription factors and (ii) bone proteins. These interactions are modeled with nonlinear differential equations using Michaelis-Menten and Hill functions. Compared to empirical evidence - coming from osteoblasts culture -, the two best systems (among 12=2,985,984 possibilities) use factors of inhibition from the start of the activation of each gene. It reveals negative indirect interactions coming from either negative feedback loops or the recently depicted micro-RNAs. The difference between the two systems also lies in the BSP equation and two ways for activating and reducing its production. Thus, it highlights the critical role of BSP in the bone GRN that acts on bone mineralization. Our study provides the first theoretical evidence of osteoblast self-inhibition after activation of the genetic regulatory network controlling mineralization with this work.
骨骼是一种通过在基因调控网络(GRN)监测下的自我组装过程构建的软硬生物材料。本文旨在通过数学模型来捕捉控制矿化的骨骼 GRN 部分的行为。在这里,我们提供了关于基因编码(i)转录因子和(ii)骨蛋白之间相互作用的经验证据的高级综述。这些相互作用使用 Michaelis-Menten 和 Hill 函数的非线性微分方程进行建模。与来自成骨细胞培养的经验证据相比,两个最佳系统(在 12=2,985,984 种可能性中)从每个基因的激活开始就使用抑制因子。它揭示了来自负反馈回路或最近描述的 micro-RNAs 的负间接相互作用。两个系统的区别还在于 BSP 方程及其激活和减少其产生的两种方式。因此,它强调了 BSP 在骨骼 GRN 中对骨骼矿化的关键作用。通过这项工作,我们的研究首次提供了理论证据,证明在控制矿化的基因调控网络激活后,成骨细胞会自我抑制。
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